Noninvasive prenatal testing by nanopore sequencing of maternal plasma DNA: feasibility assessment.

Abstract

To the Editor: Noninvasive prenatal testing (NIPT) by maternal plasma DNA sequencing is now clinically available for screening fetal chromosomal aneuploidies; these tests have close to 99% sensitivity and 99% specificity (1). Unlike amniocentesis, maternal peripheral blood sampling does not pose any risk of miscarriage. Consequently, the clinical demand for NIPT has increased substantially since it first became commercially available in 2011. Massively parallel sequencing is a core component of most of the currently used laboratory protocols for NIPT of chromosomal aneuploidies (2). Because of the high instrumentation cost, those tests are currently performed at reference laboratories. Oxford Nanopore Technologies has developed a nanopore-based DNA sequencing platform (3). Nanopore sequencers have a comparatively low equipment cost and a small footprint. Each flow cell costs US$500–900 and can be used multiple times for up to 48 h. The sequencing speed is also relatively fast, reaching 30 bases per second from each nanopore. Such features would be advantageous for use in clinical laboratories. In this study, we assessed whether nanopore sequencing could be applied to plasma DNA analysis for NIPT. We obtained plasma samples from 4 groups of individuals recruited with informed consent and institutional approval: women pregnant with male fetuses (third trimester), women pregnant with female fetuses (third trimester), nonpregnant women, and men. …